DESCRIPTION (Adapted from applicant's description): This proposal targets the ontogeny of one specific P450, the polymorphically expressed CYP2D6, that is responsible for the biotransformation of approximately 25% of drugs used therapeutically. Specifically, it addresses the hypothesis that, within the first year of life, acquisition of CYP2D6 activity consistent with genotype is dependent upon both gestational and postconceptional age. Problems associated with studying the ontogeny of drug metabolizing enzymes in this age group will be overcome by using dextromethorphan, a safe, non-sedating antitussive agent labeled for OTC use in infants. Quantitation of dextromethorphan and its metabolite, dextrorphan, provides a direct assessment of CYP2D6 activity. Specifically, a 0.3 mg/kg test dose of dextromethorphan will be administered after the evening feed and urine will be collected overnight in diapers. The metabolic ratio of dextromethorphan to dextrorphan in the 12 hour urine collection recovered from the diapers will be used to quantitate CYP2D6 activity. Genotype analysis will indicate an individual's potential CYP2D6 activity (e.g. extensive or poor metabolizer), while longitudinal assessment of phenotype (six times over the first 12 months of life coordinated with well-baby visits) will indicate the point at which activity has matured to be consistent with the genotype.